Efficient Heck cross-coupling of 3-iodo-benzopyrones with olefins under microwave irradiation without phosphine

Article abstract of DOI:10.1016/j.tet.2012.09.017

An efficient and effective microwave-assisted Heck cross-coupling of different terminal olefins with various 3-iodo-benzopyrones including sterically hindered, electron-rich, electron-neutral, and electron-deficient is developed. It proceeded faster and g

Full text of DOI:10.1016/j.tet.2012.09.017

Tetrahedron 68 (2012) 9777e9787
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient Heck cross-coupling of 3-iodo-benzopyrones with olefins under
microwave irradiation without phosphine
*
*
Yikai Zhang, Zhiliang Lv, Hanyu Zhong, Mingfeng Zhang, Tao Zhang, Wannian Zhang , Ke Li
Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 June 2012
Received in revised form 27 August 2012
Accepted 4 September 2012
Available online 10 September 2012
An efficient and effective microwave-assisted Heck cross-coupling of different terminal olefins with
various 3-iodo-benzopyrones including sterically hindered, electron-rich, electron-neutral, and electron-
deficient is developed. It proceeded faster and generally gave good to excellent yields under microwave
irradiation, phosphine-free, and air condition. The reaction could render this method particularly at-
tractive for the efficient preparation of biologically and medicinally interesting molecules.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Heck reaction
3-Iodo-benzopyrone
Microwave
Phosphine-free
1. Introduction
reaction are necessary in traditional Heck conditions.14e18 How-
ever, the usage of phosphines in the Heck reactions was undesirable
In modern synthetic organic chemistry laboratories, metal-
catalyzed cross-coupling reactions are a group of organic syn-
thetic method primarily utilized for the formation of the carbon-
ecarbon bond and the carboneheteroatom bond. Reactions such as
the Heck, Sonogashira, Suzuki, BuchwaldeHartwig, Stille, and
Negishi reactions have been found with wide application in organic
synthesis.1e6 The palladium-catalyzed Heck coupling of aryl and
vinyl halides with olefins in the presence of a base allows a one-
step mild way for Csp2 eCsp2 bond formation, which is utilized ex-
tensively as bioactive compounds, natural products, pharmaceuti-
cals, and precursors of conjugated polymers.7,8 Therefore, the Heck
reaction has recently been the focus of attention in both the aca-
demic and industrial communities.9e11 Despite many advantages
associated with this reaction including its applicability to unac-
tivated alkenes, tolerance of water and other functional groups in
the substrate, interest in the reaction has been sporadic, largely due
to the problems of long reaction time, air- and moisture-sensitive
as they are toxic as well as air- and moisture-sensitive.19 In addition,
it could be converted to phosphine oxide species, which would
poison the catalysts leading to loss of the catalytic ability. Fur-
thermore, phosphorus compounds could also cause environmental
pollution and the simplest and cheapest Pd-catalysts are assuredly
phosphine-free systems. Consequently, various ligandless catalytic
systems have been developed. However, most of them showed poor
efficiency in palladium-catalyzed Heck reactions.20e31
Isoflavones (Fig. 1), found at high levels in soy plants, are
the most active and common in phytoestrogen and play the
various biological activities via complex mechanisms, such as
anti-viral, anti-cancer, anti-oxidative, anti-hyperglycemic, anti-
inflammatory, insecticidal, anti-fungal, anti-microbial, and protect
skin from sun damage.32e36 Furthermore, some isoflavone de-
rivatives with unsaturated bond between ring B and ring C also
presented excellent bioactivities. 3-Iodo-benzopyrone offered
chemists a convenient way of synthesizing isoflavones.37 However,
the 3-iodo-benzopyrone coupling with olefins via Heck reaction
phosphine ligand, low product yields of
a-halo-a,b-unsaturated
ketones, and an incomplete understanding of the reaction
had low product yield maybe because of the
a-iodo-a,b-un-
mechanism.12,13
saturated ketone part.38,39
Various palladium species and several ligands such as phos-
phines, phosphites, carbenes, and thioethers employed for this
O
O
* Corresponding authors. Tel.: þ86 21 81871237 (K.L.); tel.: þ86 21 81871243
(W.Z.); e-mail addresses: zhangwnk@hotmail.com (W. Zhang), proflike@sina.com
(K. Li).
Isoflavone
Fig. 1. Chemical structures of isoflavone.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.09.017

9778
Y. Zhang et al. / Tetrahedron 68 (2012) 9777e9787
To the best of our knowledge there is no literature precedent to
introduction of microwave heating method could solve the prob-
lem well. The current investigation has been focused on a study of
optimizing the condition of palladium-mediated cross-coupling
reaction of 3-iodo-benzopyrones with olefins. Thus, we recently
established the novel approach, which allowed a wide range of 3-
iodo-benzopyrones were easily prepared in excellent yields under
very mild conditions. We report herein (1) a small-scale microwave
heating Heck protocol under air, (2) phosphine-free for Heck re-
the effect of microwave irradiation on the Heck reaction of
-unsaturated ketone with olefins.
In initial investigations, we examined the microwave-promoted
a-iodo-
a,b
Heck coupling reaction of the model 3-iodo-7-methoxy-4H-chro-
men-4-one (1) and methyl acrylate (2), using PdCl2(Ph3P)2 (5 mol
%) as the catalyst, K2CO3 (2.0 equiv) as the base, and H2O/DMF (1:9)
(2.0 mL) as the solvent at the temperature of 100 ꢀC for 10 min
(Table 2, entry 1). The experiment revealed that the microwave-
assisted Heck reaction under optimal oil heating condition men-
tioned above did not proceed satisfactorily. When the temperature
was decreased to 90, 80 and 70 ꢀC, respectively, the side product (4)
disappeared and 80 ꢀC was the best temperature for the main
product (3) yield (70.0%) (Table 2, entries 2e4). According to the
analysis above, reaction time was another important factor for the
yield of compound 3 and a series of time screening experiments
action, (3) applying
a-iodo-a,b-unsaturated ketone as coupling
components in the Heck reaction with olefins, and (4) high yield,
short reaction time, and environmentally friend reaction condition.
2. Results and discussion
Compound 1 was first synthesized by a reported procedure37
(Scheme 1). In initial investigations, we examined the Heck cou-
pling reaction of the model substrate 3-iodo-7-methoxy-4H-chro-
men-4-one (1) with methyl acrylate (2), using Pd(OAc)2 (5 mol %) as
O
O
O
O
OH
b
H
a
O
OH
O
OH
O
OH
b
a
O
O
O
O
d
c
I
N
O
OH
O
O
O
1
d
c
Reagents and conditions: (a) Na, Ethyl Formate, Ethyl Ether, 0oC-r.t., 18h; (b) HOAc/HCl, reflux, 30min;
(c) Piperidine, CH3OH, reflux, 3h; (d) I2, Pyridine, CH2Cl2, r.t., 20h
Scheme 1. Synthesis of the key intermediate 1.
the catalyst, Cu(OAc)2 as base and DMF/DMSO (9:1) as solvent at
120 ꢀC for 6 h (Table 1, entry 1). A series of different solvents,
temperatures, catalysts, bases, and reaction time were screened
under nitrogen protection. As can be seen from Table 1, of the
solvents screened, H2O/DMF (1:9) showed the best result and the
corresponding coupling product 3 and byproduct 4 were obtained
in 75.3% and 3% yield, respectively (Table 1, entry 6). There were
indications that the choice of solvent had distinct impact both on
the main product yield and de-iodine byproduct yield. It was found
that if the reaction temperature was elevated to 100 ꢀC, the corre-
sponding reaction could be finished with 78% yield and the
byproduct was decreased to 0.5% yield (Table 1, entry 10), which
presented that higher temperature would lead to more side prod-
uct. When catalyst was replaced by other palladium complex such
as PdCl2(Ph3P)2, Pd2(dba)3, and Pd(Ph3P)4 (Table 1, entries 12e14),
results showed that the reaction did not work with Pd2(dba)3 and
Pd(Ph3P)4. However, PdCl2(Ph3P)2 was found slightly better than
Pd(OAc)2. Furthermore, other bases like Na2CO3, NaOH, K2CO3,
pyridine, and triethylamine were used and K2CO3 showed the best
result (Table 1, entry 17). Finally, reaction time was adjusted to 4, 8,
10 and 12 h, respectively. The results showed that 6 h was exactly
the best reaction time for the main product yield (Table 1, entries
20e23).
Table 1
Synthesis of compound 3 under oil heatinga
Entry Solvent
Catalyst
Base
Temp Time Yieldb
(ꢀC)
(h)
3/4 (%)
1
2
3
4
5
6
7
8
DMF/DMSO¼9:1 Pd(OAc)2
Cu(OAc)2 120
Cu(OAc)2 120
Cu(OAc)2 120
Cu(OAc)2 120
Cu(OAc)2 120
Cu(OAc)2 120
Cu(OAc)2 120
Cu(OAc)2 130
Cu(OAc)2 110
Cu(OAc)2 100
6
6
6
6
6
6
6
6
6
6
6
6
6
70.5:5
54.0:1
69.5:1.6
12.0:0
67.0:3.6
75.3:3
66.5:1.2
69.0:10
71.0:2
78.0:0.5
50.0:0
80.1:0
0:0
DMF
DMSO
CH3CN
THF
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
H2O/DMF¼1:9
H2O/DMF¼5:5
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Cu(OAc)2
90
PdCl2(Ph3P)2 Cu(OAc)2 100
Pd2(dba)3
Pd(Ph3P)4
Cu(OAc)2 100
Cu(OAc)2 100
6
0:0
The results above indicate that high temperature (ꢁ100 ꢀC) and
long time (ꢁ6 h) would cause de-iodine byproduct. The main
product yield was also influenced by solvent, catalyst, and base.
Thus, the optimal reaction condition was using PdCl2(Ph3P)2 (5 mol
%) as the catalyst, K2CO3 (2.0 equiv) as the base, and H2O/DMF (1:9)
(2.0 mL) as the solvent at the temperature of 100 ꢀC for 6 h.
Table 1 showed that high temperature was helpful to the main
product (3) yield and low temperature could avoid generating de-
iodine compound (4), which made it difficult to conclude the best
temperature for this reaction. Enlightened by the different heating
principle between oil heating and microwave heating,40 the
PdCl2(Ph3P)2 Na2CO3
PdCl2(Ph3P)2 NaOH
PdCl2(Ph3P)2 K2CO3
PdCl2(Ph3P)2 Pyridine
PdCl2(Ph3P)2 TEA
PdCl2(Ph3P)2 K2CO3
PdCl2(Ph3P)2 K2CO3
PdCl2(Ph3P)2 K2CO3
PdCl2(Ph3P)2 K2CO3
100
100
100
100
100
100
100
100
100
6
6
6
6
6
4
8
10
12
72.3:0
11.0:0
84.7:0.1
65.3:0
62.1:0
60.8:0
85:0.5
84:0.1
85:0.1
a
Unless otherwise specified, all reactions were performed with compound 1
(4 mmol), methyl acrylate (4.8 mmol), catalyst (5 mmol %), and base (8 mmol) in
solvent (50 mL) via oil heating.
b
Isolated yield.

Y. Zhang et al. / Tetrahedron 68 (2012) 9777e9787
9779
Table 2
acidic group were unfavorable to this type reaction. (Table 3, entries
5, 6, and 8). Notably, although electron-withdrawing group or
electron-donating groups with olefins were applied and the re-
action could be smoothly performed, an electron-donating group
was more favored than an electron-withdrawing group. Further-
more, the presence of hydroxy group on the benzopyrone led to
slightly decreased yields (Table 3, entries 18e23) as a consequence
of weak acidic of the phenol. It is noted that the existence of strong
electron-withdrawing group such as nitro-group on the benzene
ring of the benzopyrone would hinder the reaction procedure and
no product could be observed (Table 3, entry 24).
Synthesis of compound 3 under microwave heatinga
Entry
Solvent
Catalyst
Base
Temp
(ꢀC)
Time
(min)
Yieldb
3/4 (%)
1
2
3
4
5
6
7
8
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
H2O/DMF¼1:9
DMF
PdCl2(Ph3P)2
PdCl2(Ph3P)2
PdCl2(Ph3P)2
PdCl2(Ph3P)2
PdCl2(Ph3P)2
PdCl2(Ph3P)2
PdCl2(Ph3P)2
PdCl2(Ph3P)2
PdCl2(Ph3P)2
PdCl2(Ph3P)2
PdCl2(Ph3P)2
PdCl2(Ph3P)2
PdCl2(Ph3P)2
PdCl2(Ph3P)2
PdCl2(Ph3P)2
PdCl2(Ph3P)2
PdCl2(Ph3P)2
PdCl2(Ph3P)2
Pd(OAc)2
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
NaOH
TEA
Pyridine
TEA
TEA
TEA
TEA
100
90
80
70
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
10
10
10
10
11
8
6
5
4
5
5
5
5
5
5
5
5
5
67.3:2
70.6:0
70.0:0
54.0:0
70.1:0
70.6:0
69.9:0
70.5:0
36.9:0
59.1:0
23.4:0
81.3:0
79.6:0
90.9:0
81.8:0
10.2:0
0:0
Reactions of various 3-iodine flavonoid derivatives with differ-
ent olefins under the modified optimal conditions were explored to
further probe the scope of the process (Table 4). Although, the steric
hindrance effect of the benzene ring at b-position of the a-iodo-a,b-
9
unsaturated ketone might be the key reason for the difficulty of the
Heck reaction, both reaction temperature and time regulation
(110 ꢀC and 90 min) could result in generation of desired func-
tionalized flavonoid in moderate to good yields (Table 4). Likewise,
the electronic effects of substituents on the olefins affected the
reactions and it is clear that an electron-donating group will in-
crease the reactivity of the double bond. Notably, heterocyclic
compounds appeared to have lower yield than benzene ring and
alkyl groups (Table 4, entries 22e24). Clearly, the phenolic hydroxyl
group on the flavonoid also strongly contributed to the yield de-
crease of the Heck coupling reaction (Table 4, entries 14e24).
Despite the merits of palladium-catalyzed coupling reactions
with phosphine-free condition have been known to all, researches
to disclose the mechanism of reactions under ‘phosphineless’
conditions are more challenging than those of systems reacting
through phosphine and carbene ligands. Based on the reports
published concerning investigations of the mechanistic path-
way,42,43 a tentative mechanism for the Heck reaction is proposed
in Scheme 2. First, palladium(II) acetate with triethylamine resulted
in the conversion of the palladium complex to [Pd2I6][NEt3H]2 (A)
in step 1. [Pd2I6]2ꢂ is a well known counter-ion,35 which inserted
itself to carbon iodine bond (B) according to an oxidative addition
reaction (step 2). Intermediate C was then transformed into a sol-
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
DMSO
CH3CN
EtOH
H2O
TEA
TEA
0:0
DMF
5
5
5
5
4
6
93.5:0
85.6:0
0:0
0:0
80.6:0
93.1:0
DMF
DMF
PdCl2(dppf)2
Pd(Ph3P)4
TEA
TEA
DMF
Pd2(dba)3
TEA
DMF
Pd(OAc)2
TEA
DMF
Pd(OAc)2
TEA
a
Unless otherwise specified, all reactions were performed with compound 1
(4 mmol), methyl acrylate (4.8 mmol), catalyst (5 mmol %), and base (8 mmol) in
solvent (50 mL) via microwave heating.
b
Isolated yield.
showed that 5 min was the best one for the reaction (Table 2, en-
tries 5e9). Moreover, base selection experiment proved that when
the inorganic bases were substituted by organic bases, the yield of
main product was augmented and the triethylamine (TEA) was the
best choice (Table 2, entries 10e13). Considering the alteration of
base from inorganic to organic one, the solvent also needs to be
changed correspondingly. Thereby, solvents such as DMF, DMSO,
CH3CN, EtOH, and H2O were used, respectively, and the results
showed that DMF could drastically boost the desired compound
yield (90.9%) (Table 2, entries 14e18) and on the contrary, pure
water was certificated to be negative for this reaction (Table 2, entry
18). Furthermore, Pd(OAc)2 displayed superiority over the other
palladium catalysts (Table 2, entries 19e22). Finally, due to the
reaction conditions regulation, we considered that the reaction
time adjustment might be helpful to increase product yield. Nev-
ertheless, the results showed that neither adding nor decreasing
the time was necessary (Table 2, entries 23 and 24).
vated structure (D) in step 3. The
p-complex formation of palla-
dium with methyl acrylate in step 4 enabled the alkene inserted
itself between the PdeC bond in a syn-insertion step (step 5).
Subsequently, an internal rotation happened due to the torsional
strain in step 6 and step 7 was a b-hydride elimination step (gen-
eration of trans-double bond) with the formation of desired
product H. At the same time, the palladium complex (A) was
regenerated via reductive elimination of the palladiumeiodine
complex (I) by triethylamine in the final step 8.
The analysis of 1H NMR spectrum of all of the final products
showed the doublet of olefins observed with coupling constant (J)
from 14.7 to 16.4 Hz of two olefinic protons confirmed the trans-
double bond, which could be one of the proof of our hypothetic
mechanism.
Thereby, the optimal reaction conditions under microwave ir-
radiation were using Pd(OAc)2 (5 mol %) as the catalyst, TEA
(2.0 equiv) as the base, and DMF (2.0 mL) as the solvent at the
temperature of 80 ꢀC for 5 min.
3. Conclusion
Under the optimized reaction conditions, the generality of the
reaction was investigated by using 3-iodo-7-methoxy-4H-chro-
men-4-one/7-hydroxy-3-iodo-4H-chromen-4-one and a variety of
olefins to produce benzopyrone derivatives. The results are sum-
marized in Table 3. The findings showed that these reactions led to
production of the corresponding chromone derivatives in moderate
to excellent yields (Table 3). Reaction of compound 1 with allyl
alcohol (Table 3, entry 2) gave complicated products, and (E)-3-(7-
methoxy-4-oxo-4H-chromen-3-yl) acrylaldehyde was found to be
the major product in 59.6% yield, which appeared to be reasonable
according to the report.41 Moreover, it is clear that olefins with
In summary, we have developed an efficient, mild, and
phosphine-free Heck reaction of
a-iodo-a,b-unsaturated ketone
with different olefins under microwave irradiation to provide the
desired products in minutes. Our reaction condition was as follows:
5 mol % of Pd(OAc)2 as catalyst, DMF as solution, and triethylamine
as base. The short reaction times and simple reaction conditions
coupled with a broad spectrum of olefins render this method par-
ticularly attractive for the efficient preparation of biologically and
medicinally interesting molecules. The developed Heck method
was worth to drawing attention due to the convenient, non-ex-
pensive, and environmentally friendly experimental procedure

9780
Y. Zhang et al. / Tetrahedron 68 (2012) 9777e9787
Table 3
Synthesis of compounds 5ae5xa
Entry
1
R1
R2
H
R3
Product
Yieldb (%)
94.2
Entry
13
R1
R2
H
R3
Product
Yieldb (%)
77.8
OCH3
5a
OCH3
5m
2
3
OCH3
OCH3
H
H
5bc
5c
59.6
21.8
14
15
OCH3
OCH3
H
H
5n
5o
74.6
73.4
4
5
6
7
OCH3
OCH3
OCH3
OCH3
H
H
H
H
5d
5e
5f
47.6
16
17
18
19
OCH3
OCH3
OH
H
H
H
H
5p
5q
5r
5s
81.8
83.1
88.9
86.3
dd
dd
5g
85.7
OH
8
OCH3
H
5h
dd
20
OH
H
5t
71.6
9
OCH3
OCH3
H
H
5i
5j
90.3
78.0
21
22
OH
OH
H
H
5u
5v
76.8
72.6
10
11
OCH3
OCH3
H
H
5k
5l
10.5
8.1
23
24
OH
H
5w
5x
77.2
12
OCH3
NO2
dd
a
Unless otherwise specified, all reactions were performed with 3-iodine chromone (4 mmol), olefin (4.8 mmol), Pd(OAc)2 (5 mmol %) and Et3N (8 mmol) in DMF (50 mL).
Isolated yield.
b
c
The main product of 5b was
.
d
‘d’ means no product was observed.
under air and could be readily adopted to prepare large libraries,
and the versatility of this methodology is suitable for library syn-
thesis in drug discovery efforts.
Avance 600 instruments and samples were obtained in CDCl3
(referenced to residual CHCl3 at 7.26 ppm for 1H and 77.0 ppm for
13C) or DMSO-d6 (referenced to residual DMSO at 2.50 ppm for 1H
and 39.5 ppm for 13C). Coupling constants (J) are in hertz. The
multiplicities of the signals are described using the following ab-
4. Experimental section
4.1. General
breviations:
s¼singlet,
d¼doublet,
t¼triplet,
q¼quartet,
m¼multiplet, br¼broad. Mass spectra were recorded using Finigan
LCQ Deca XP MAX mass spectrometer. Yields refer to quantities
obtained after chromatography. Elemental analyses were per-
formed with a MOD-1106 instrument and were consistent with
theoretical values within 0.4%.
All reactions were carried out in an oven-dried glassware.
Progress of reactions was monitored by thin layer chromatography
(TLC) while purification of crude compounds was done by column
chromatography using silica gel (200e300 mesh). Microwave ir-
radiation was performed with Sineo MAS-II microwave synthesis
workstation. Melting points were recorded on a YUHUA X-5
melting point apparatus and are uncorrected. Elemental analysis
was performed with a Carlo Erba 1106 elemental analyzer. NMR
experiments were performed on Bruke Avance 300 and Bruke
4.2. General experimental procedure for Heck reaction under
oil heating condition
To
a solution of 3-iodo-7-methoxy-4H-chromen-4-one (1)
(4 mmol) and methyl acrylate (2) (4.8 mmol) in solvent was added

Y. Zhang et al. / Tetrahedron 68 (2012) 9777e9787
Table 4 (continued )
9781
Table 4
Synthesis of compounds 6ae6xa
Entry
R1
R2
R3
R4
Product
Yieldb (%)
21
H
OH
OH
6u
60.3
41.5
58.8
40.7
22
23
H
H
H
OH
OH
OH
OH
OH
OH
6v
6w
6x
Entry
1
R1
H
R2
R3
R4
Product
Yieldb (%)
79.6
OCH3
OCH3
6a
24
2
3
4
5
6
H
H
H
H
H
OCH3
OCH3
OCH3
H
OCH3
OCH3
OCH3
H
6b
6c
6d
6e
6f
82.7
85.0
80.9
75.3
60.4
a
Unless otherwise specified, all reactions were performed with 3-iodine flavo-
noid (4 mmol), olefin (4.8 mmol), Pd(OAc)2 (5 mmol %) and Et3N (8 mmol) in DMF
(50 mL).
b
Isolated yield.
catalyst (5 mmol %) and base (8 mmol). The reaction mixture was
stirred via oil heating under nitrogen protection. Then the mixture
was poured into 10% HCl ice-water (300 mL) slowly with stirring.
The suspension was filtered through a filter and filter cake was
collected and dried. The crude product was purified by chroma-
tography over silica gel to give compound 3 or 4.
OCH3
OCH3
7
H
OCH3
OCH3
6g
68.0
4.2.1. (E)-Methyl 3-(5-hydroxy-7-methoxy-4-oxo-4H-chromen-3-yl)
acrylate (3). Color: yellow; mp: 176.5e177.6 ꢀC; 1H NMR:
(300 MHz, CDCl3) d: 3.78 (s, 3H, CH3), 3.86 (s, 3H, CH3eO), 6.84 (d,
1H, J¼3 Hz, AreH), 7.02e7.05 (dd, 1H, J1¼2.4 Hz, J2¼2.4 Hz, AreH),
7.24 (d, 1H, J¼15.9 Hz, O]CeCH]C), 7.37 (d, 1H, J¼15.9 Hz, O]
CeC]CH), 8.04 (s, 1H, OeCH]C), 8.16 ppm (d, 1H, J¼9 Hz, AreH);
8
9
H
OCH3
OCH3
OCH3
H
6h
6i
66.7
81.2
13C NMR (75 MHz, DMSO-d6)
d: 51.40, 55.85, 101.31, 115.85, 116.64,
OCH3
117.65, 119.45, 127.82, 136.07, 156.91, 159.78, 162.94, 167.01,
174.49 ppm; ESI-MS (m/z): 261.11 (Mþ1)þ. Anal. (C14H12O5): C
64.61, H 4.65. Found: C 64.65, H 4.67%.
10
OCH3
OCH3
H
6j
83.5
4.2.2. 7-Methoxy-4H-chromen-4-one (4). Color: white; mp:
105.4e106.0 ꢀC; 1H NMR: (300 MHz, CDCl3)
d: 3.90 (s, 3H, CH3eO),
11
12
OCH3
OCH3
OCH3
OCH3
H
H
6k
6l
55.8
64.4
6.28 (d, J¼6.3 Hz, 1H, O]CeCH]C), 6.84 (d, 1H, J¼4 Hz, AreH),
7.02e7.05 (dd, 1H, J1¼2.4 Hz, J2¼2.4 Hz, AreH), 7.78 (d, 1H, AreH,
J¼6.3 Hz, O]CeCH]C), 8.12 ppm (d, 1H, J¼9 Hz, AreH); 13C NMR
(75 MHz, CDCl3) d: 55.2, 102.6, 107.5, 110.6, 116.2, 128.7, 142.1, 157.6,
163.2, 179.6 ppm; ESI-MS (m/z): 177.06 (Mþ1)þ. Anal. (C10H8O3): C
68.18, H 4.58. Found: C 68.22, H 4.57%.
13
OCH3
OCH3
H
6m
68.0
4.3. General experimental procedure for Heck reaction under
microwave heating condition
14
15
16
H
H
H
OH
OH
OH
OH
OH
OH
6n
6o
6p
73.5
77.6
77.5
To
a solution of 3-iodo-chromone (4 mmol) and olefin
(4.8 mmol) in solvent was added catalyst (5 mmol %) and base
(8 mmol). The reaction mixture was stirred via microwave heating
under air. Then the mixture was poured into 10% HCl ice-water
(300 mL) slowly with stirring. The suspension was filtered
through a filter and filter cake was collected and dried. The crude
product was purified by chromatography over silica gel to give
resulting product.
17
18
H
H
OH
OH
OH
OH
6q
6r
72.8
48.1
4.3.1. (E)-Ethyl
(5a). Color: pink; mp: 139.3e139.7 ꢀC; 1H NMR: (300 MHz,
CDCl3) : 1.30e1.35 (t, 3H, CH3), 3.92 (s, 3H, CH3eO), 4.22e4.29
3-(7-methoxy-4-oxo-4H-chromen-3-yl)acrylate
d
19
20
H
H
OH
OH
OH
OH
6s
53.3
(q, 2H, CH2), 6.85 (d, 1H, J¼2.4 Hz, AreH), 6.99e7.03 (dd, 1H,
J1¼2.4 Hz, J2¼2.4 Hz, AreH), 7.27 (d, 1H, J¼15.9 Hz, O]CeCH]
C), 7.40 (d, 1H, J¼15.9 Hz, O]CeC]CH), 8.04 (s, 1H, OeCH]C),
6t
55.9
8.18 ppm (d, 1H, J¼9 Hz, AreH); 13C NMR (75 MHz, DMSO-d6)
d:
(continued on next page)

9782
Y. Zhang et al. / Tetrahedron 68 (2012) 9777e9787
Scheme 2. Putative reaction mechanism.
14.22, 55.85, 101.33, 56.31, 115.83, 116.45, 117.60, 119.25, 127.82,
135.76, 156.90, 159.78, 162.94, 167.01, 174.28 ppm; ESI-MS (m/z):
275.09 (Mþ1)þ. Anal. (C15H14O5): C 65.69, H 5.15. Found: C
65.72, H 5.47%.
ESI-MS (m/z): 232.08 (Mþ1)þ. Anal. (C13H13NO3): C 67.52, H 5.67, N
6.06. Found: C 67.95, H 5.29, N 6.06%.
4.3.5. (E)-7-Methoxy-3-styryl-4H-chromen-4-one (5g). Color: yel-
low; mp: 134.1e135.0 ꢀC; 1H NMR: (300 MHz, CDCl3)
d: 3.91 (s, 3H,
4.3.2. 3-(7-Methoxy-4-oxo-4H-chromen-3-yl)propanal (5b). Color:
CH3eO), 6.84 (d, 1H, J¼2.2 Hz, AreH), 6.98 (d, 1H, J¼16.2 Hz,
AreCH]C), 6.93e7.03 (dd, 1H, J1¼9.2 Hz, J2¼2.2 Hz, AreH),
7.26e7.37 (m, 3H, AreH), 7.50e7.53 (m, 2H, AreH), 7.63 (d, 1H,
J¼16.2 Hz, AreC]CH), 8.04 (s, 1H, OeCH]C), 8.21 (d, 1H, J¼9.2 Hz,
yellow; mp: 125.5e126.1 ꢀC; 1H NMR: (300 MHz, DMSO-d6)
d:
2.57e2.62 (t, 2H, CH2eCH2), 2.68e2.73 (t, 2H, CH2eC]O), 3.67 (s,
3H, CH3eO), 7.00e7.05 (m, 2H, AreH), 7.90e7.9 4 (dd, 1H, J1¼1.5 Hz,
J2¼1.8 Hz, AreH), 8.17 (s, 1H, OeCH]C), 9.70 ppm (s, 1H, CHO); 13
C
AreH); 13C NMR (75 MHz, CDCl3)
d: 55.8, 100.1, 114.7, 118.3, 119.2,
NMR (75 MHz, DMSO-d6)
d
: 20.34, 40.64, 55.83, 100.20, 114.22,
121.7, 126.6, 127.6, 127.8, 128.6, 131.5, 137.4, 152.5, 157.6, 164.0,
176.0 ppm; ESI-MS (m/z): 278.30 (Mþ1)þ. Anal. (C18H14O3): C 77.68,
H 5.07. Found: C 77.19, H 5.17%.
116.01, 124.04, 127.64, 154.61, 158.2, 164.13, 176.53, 202.11 ppm; ESI-
MS (m/z): 233.08 (Mþ1)þ. Anal. (C13H12O4): C 67.23, H 5.21. Found:
C 67.62, H 5.82%.
4.3.6. (E)-3-(4-Ethoxystyryl)-7-methoxy-4H-chromen-4-one
4.3.3. (E)-3-(7-Methoxy-4-oxo-4H-chromen-3-yl)acrylonitrile
(5i). Color: yellow; mp: 147.6e148.4 ꢀC; 1H NMR: (500 MHz,
CDCl3) d: 1.43 (t, 3H, CH3eCeO), 3.91 (s, 3H, CH3eO), 4.06 (q, 2H,
(5c). Color: yellow; mp: 223.6e224.3 ꢀC; 1H NMR: (300 MHz,
CDCl3)
d
: 3.90 (s, 3H, CH3eO), 6.98 (d, 1H, J¼2.4 Hz, AreH),
CH2eO), 6.84 (d, 1H, J¼2.4 Hz, AreH), 6.85 (d, 1H, J¼16.4 Hz,
AreCH]C), 6.88 (d, 2H, J¼8.7 Hz, AreH), 6.93e7.03 (dd, 1H,
J1¼8.9 Hz, J2¼2.4 Hz, AreH), 7.43e7.45 (m, 2H, AreH), 7.51 (d, 1H,
J¼16.4 Hz, AreC]CH), 8.03 (s, 1H, OeCH]C), 8.20 (d, 1H, J¼8.9 Hz,
6.08e7.14 (dd, 1H, J1¼1.8 Hz, J2¼1.8 Hz, AreH), 7.23 (d, 1H,
J¼15.9 Hz, C]CHeCeN), 7.35 (d, 1H, J¼15.9 Hz, CH]CeCeN), 8.01
(s, 1H, OeCH]C), 8.70 ppm (d, 1H, J¼9 Hz, AreH); 13C NMR
(75 MHz, CDCl3)
d: 55.84, 92.53, 100.11, 114.22, 115.84, 116.24,
AreH); 13C NMR (75 MHz, CDCl3)
d: 14.8, 55.8, 63.4, 100.0, 114.6,
123.64, 127.81, 149.35, 150.43, 158.24, 1675.12, 121.55 ppm; ESI-MS
(m/z): 228.06 (Mþ1)þ. Anal. (C13H9NO3): C 68.72, H 3.99, N 6.16.
Found: C 68.41, H 3.55, N 6.23%.
116.7, 117.6, 118.3, 119.3, 121.9, 127.8, 130.0, 131.0, 152.0, 157.2, 158.8,
163.9, 176.1 ppm; ESI-MS (m/z): 322.11 (Mþ1)þ. Anal. (C18H14O3): C
74.52, H 5.63. Found: C74.58, H 5.79%.
4.3.4. (E)-3-(3-Aminoprop-1-enyl)-7-methoxy-4H-chromen-4-one
4.3.7. (E)-3-(3-Fluorostyryl)-7-methoxy-4H-chromen-4-one
(5d). Color: yellow; mp: 136.6e137.4 ꢀC; 1H NMR: (300 MHz,
(5j). Color: Yellow; mp: 193.5e194.3 ꢀC; 1H NMR: (300 MHz,
DMSO-d6)
d: 1.23 (s, 2H, NH2), 3.36 (s, 2H, CH2eN), 3.85 (s, 3H,
CDCl3) d: 3.91 (s, 3H, CH3eO), 6.85e7.02 (m, 4H, AreH, AreCH]C),
CH3eO), 5.86e5.97 (m, 1H, C]CHeCeN), 6.74e6.77 (dd, 1H,
J1¼2.1 Hz, J2¼2.1 Hz, AreH), 6.81 (s, 1H, OeCH]C), 6.90 (d, 1H,
J¼15.6 Hz, CH]CeCeN), 7.52 (d, 1H, ArH), 7.80 ppm (d, 1H, ArH);
7.25e7.27 (m, 1H, AreH), 7.67 (d, 1H, J¼16.2 Hz, AreC]CH), 8.04 (s,
1H, OeCH]C), 8.10e8.13 (m, 1H, AreH), 8.21 (d, 1H, J¼9.2 Hz,
AreH), 8.35e8.40 ppm (t, 1H, AreH); 13C NMR (75 MHz, CDCl3)
d:
55.94, 100.16, 113.23, 115.71, 116.33, 120.64, 122.78, 123.43, 127.64,
129.46, 131.98, 132.61, 139.46, 146.21, 155.02, 157.57, 165.32,
13C NMR (75 MHz, DMSO-d6)
d
: 43.87, 55.84, 100.13, 114.43, 116.53,
120.23, 125.32, 127.84, 133.45, 149.34, 163.26, 167.41, 120.34 ppm;

Y. Zhang et al. / Tetrahedron 68 (2012) 9777e9787
9783
175.13 ppm; ESI-MS (m/z): 297.09 (Mþ1)þ. Anal. (C18H13FO3): C
1H, NH), 6.85e6.90 (dd, 1H, J1¼2.4 Hz, J2¼2.4 Hz, AreH), 6.98e7.03
(m, 1H, AreH), 7.28e7.37 (m, 6H, AreH, O]CeCH]C), 7.74 (d, 1H,
J¼15 Hz, O]CeC]CH), 8.03 (s, 1H, OeCH]C), 8.16 ppm (d, 1H,
72.97, H 4.42. Found: C 73.02, H 4.20%.
4.3.8. (E)-7-Methoxy-3-(4-nitrostyryl)-4H-chromen-4-one
J¼9 Hz, AreH); 13C NMR (75 MHz, CDCl3)
d: 43.01, 55.87, 100.20,
(5k). Color: yellow; mp: 173.1e174.6 ꢀC; 1H NMR: (300 MHz,
115.20, 116.45, 119.11, 125.74, 126.01, 127.82, 129.33, 129.44, 130.05,
135.54, 150.65, 157.85, 164.54, 166.25, 175.79 ppm; ESI-MS (m/z):
336.12 (Mþ1)þ. Anal. (C20H17NO4): C 71.63, H 5.11, N 4.18. Found: C
71.56, H 5.20, N 4.15%.
CDCl3)
d
: 3.95 (s, 3H, CH3eO), 6.89 (d, 1H, J¼2.4 Hz, AreH),
7.04e7.06 (dd, 1H, J1¼8.8 Hz, J2¼2.4 Hz, AreH), 7.08 (d, 1H,
J¼16.2 Hz, AreCH]C), 7.66 (d, 2H, J¼8.8 Hz, AreH), 7.80e7.85 (m,
1H, AreH), 7.87 (d, 1H, J¼16.2 Hz, AreC]CH), 8.10 (s, 1H, OeCH]
C), 8.23 (d, 1H, J¼8.9 Hz, AreH) ,8.35e8.39 ppm (t, 1H, AreH); 13C
4.3.14. (E)-N-(4-Fluorophenethyl)-3-(7-methoxy-4-oxo-4H-chro-
NMR (75 MHz, CDCl3)
d: 55.9, 100.2, 115.0, 118.0, 120.7, 124.0, 126.9,
men-3-yl)acrylamide (5q). Color: yellow; mp: 177.5e178.5 ꢀC; 1H
127.6, 129.4, 144.1, 146.8, 154.2, 157.5, 164.2, 175.8 ppm; ESI-MS (m/
z): 324.08 (Mþ1)þ. Anal. (C18H13NO5): C, 66.87; H 4.05, N 4.33.
Found: C 66.85, H 4.09, N 4.30%.
NMR: (300 MHz, CDCl3) d: 2.83e2.87 (m, 2H, CH2eAr) 3.60e3.66
(m, 2H, CH2eN), 3.92(s, 3H, CH3eO), 5.70 (s, 1H, NH), 6.86 (d, 1H,
J¼2.1 Hz, AreH), 6.99e7.03 (m, 3H, AreH), 7.15e7.20 (m, 2H, AreH),
7.27 (d, 1H, J¼15 Hz, O]CeCH]C), 7.45 (d, 1H, J¼15 Hz, O]CeC]
CH), 8.03 (s, 1H, OeCH]C), 8.15 ppm (d, 1H, J¼8.7 Hz, AreH); 13C
4.3.9. (E)-7-Methoxy-3-(3-nitrostyryl)-4H-chromen-4-one
(5l). Color: yellow; mp: 173.1e174.6 ꢀC; 1H NMR: (300 MHz, CDCl3)
NMR (75 MHz, CDCl3) d: 35.30, 40.75, 55.40, 100.11, 114.99, 115.13,
d
: 3.93 (s, 3H, CH3eO), 6.87 (d, 1H, J¼2.4 Hz, AreH), 7.00e7.02 (dd,
116.45, 119.03, 123.35, 127.54, 131.00, 135.53, 141, 156.32, 158.44,
161.78, 166.32, 167.11, 177.83 ppm; ESI-MS (m/z): 368.13 (Mþ1)þ.
Anal. (C21H18FNO4): C 68.66, H 4.94, N 3.81. Found: C 68.70, H 5.00,
N 3.85%.
1H, J1¼8.9 Hz, J2¼2.4 Hz, AreH), 7.03 (d, 1H, J¼16.3 Hz, AreCH]C),
7.50e7.52 (t, 1H, AreH), 7.78e7.82 (m, 1H, AreH), 7.85 (d, 1H,
J¼16.3 Hz, AreC]CH), 8.08 (s, 1H, OeCH]C), 8.10e8.12 (m, 1H,
AreH), 8.21 (d, 1H, J¼8.9 Hz, AreH), 8.35e8.39 ppm (t, 1H, AreH);
13C NMR (75 MHz, CDCl3)
d
: 55.9, 100.2, 114.9, 115.5, 118.34, 120.6,
4.3.15. (E)-Methyl
(5r). Color: yellow; mp: 221.7e222.0 ꢀC; 1H NMR: (300 MHz,
DMSO-d6)
3-(7-hydroxy-4-oxo-4H-chromen-3-yl)acrylate
122.2, 122.5, 127.6, 129.4, 129.6, 132.6, 139.4, 146.2, 153.9, 157.5,
166.3, 175.1 ppm; ESI-MS (m/z): 324.08 (Mþ1)þ. Anal. (C18H13NO5):
C, 66.87; H 4.05, N 4.33. Found: C 66.85, H 4.07, N 4.31%.
d
: 3.70 (s, 3H, CH3), 6.89 (d, 1H, J¼2.1 Hz, AreH), 6.97 (dd,
1H, J1¼2.1 Hz, J2¼2.1 Hz, AreH), 7.18 (d, 1H, J¼15.9 Hz, O]CeCH]
C), 7.45 (d, 1H, J¼15.9 Hz, O]CeC]CH), 7.96 (d, 1H, J¼8.7 Hz,
AreH), 8.76 (s, 1H, OeCH]C), 10.93 ppm (s, 1H, OH); 13C NMR
4.3.10. (E)-3-(7-Methoxy-4-oxo-4H-chromen-3-yl)-N-phenyl-
acrylamide (5m). Color: yellow; mp: 222.5e223.9 ꢀC; 1H NMR:
(75 MHz, DMSO-d6) d: 51.41, 102.43, 115.69, 116.21, 117.57, 119.44,
(300 MHz, CDCl3)
d
: 3.93 (s, 3H, CH3eO), 6.87 (d, 1H, J¼3 Hz, AreH),
127.25, 136.85, 156.89, 159.62, 163.01, 166.94, 174.48 ppm; ESI-MS
(m/z): 247.06 (Mþ1)þ. Anal. (C13H10O5): C 63.42, H 4.09. Found: C
63.41, H 4.14%.
7.02e7.05 (dd, 2H, J1¼2.4 Hz, J2¼2.4 Hz, AreH), 7.30e7.43 (m, 5H,
AreH, O]CeCH]C), 7.72 (d, 1H, J¼12 Hz, O]CeC]CH), 8.09 (s,
1H, OeCH]C), 8.19 ppm (d, 1H, J¼9 Hz, AreH); 13C NMR (75 MHz,
CDCl3)
d
: 55.83, 100.16, 114.95, 116.48, 119.56, 120.36, 121.01, 127.55,
4.3.16. (E)-Ethyl
(5s). Color: brown; mp: 264.5e264.9 ꢀC; 1H NMR: (300 MHz,
DMSO-d6) : 1.23 (m, 3H, CH3eCH2), 4.16 (m, 2H, CH3eCH2), 6.88 (d,
3-(7-hydroxy-4-oxo-4H-chromen-3-yl)acrylate
128.32, 128.64, 133.86, 137.20, 140.63, 149.64, 157.26, 157.77,
164.74 ppm; ESI-MS (m/z): 322.11 (Mþ1)þ. Anal. (C19H15NO4): C
71.02, H 4.71, N 4.36. Found: C 71.00, H 4.79, N 4.44%.
d
1H, J¼2.1 Hz, AreH), 6.94 (m, 1H, AreH), 7.15 (d, 1H, J¼15.9 Hz, O]
CeCH]C), 7.43 (d,1H, J¼15 Hz, O]CeC]CH), 7.95 (d,1H, J¼8.7 Hz,
AreH), 8.74 (s, 1H, OeCH]C), 10.93 ppm (s, 1H, OH); 13C NMR
4.3.11. (E)-3-(7-Methoxy-4-oxo-4H-chromen-3-yl)-N-(4-
methoxyphenyl)acrylamide
(5n). Color:
yellow;
: 3.81 (s, 3H, CH3eO),
mp:
(75 MHz, DMSO-d6) d: 14.16, 59.80, 102.75, 116.31, 116.52, 117.93,
236.3e236.8 ꢀC; 1H NMR: (300 MHz, CDCl3)
d
119.05, 128.22, 136.20, 156.78, 158.80, 162.86, 166.74, 174.20 ppm;
ESI-MS (m/z): 261.07 (Mþ1)þ. Anal. (C14H12O5): C 64.61, H 4.65.
Found: C 64.61, H 4.62%.
3.93 (s, 3H, CH3eO), 6.87e6.90 (m, 2H, AreH), 7.02 (dd, 2H,
J1¼2.4 Hz, J2¼2.4 Hz, AreH), 7.36 (s, 1H, AreH), 7.36 (d, 1H,
J¼14.7 Hz, O]CeCH]C), 7.54 (d, 1H, J¼9 Hz, AreH), 7.70 (d, 1H,
J¼15 Hz, O]CeC]CH), 8.06 (d,1H, J¼3 Hz, OeCH]C), 8.19 ppm (d,
4.3.17. (E)-3-(7-Hydroxy-4-oxo-4H-chromen-3-yl)-N-phenyl-
1H, J¼9 Hz, AreH); 13C NMR (75 MHz, CDCl3)
d
: 56.74, 101.50,
acrylamide (5t). Color: yellow; mp: 282.8e229.1 ꢀC; 1H NMR:
114.97, 115.45, 116.40, 119.34, 120.32, 122.75, 126.51, 128.90, 134.16,
150.23, 158.50, 159.04, 165.59, 166.43, 166.99, 175.16 ppm; ESI-MS
(m/z): 352.11 (Mþ1)þ. Anal. (C20H17NO5): C 68.37, H 4.88, N 3.99.
Found: C 68.41, H 4.74, N 3.95%.
(300 MHz, DMSO-d6)
d
: 6.86 (d, 1H, J¼2.1 Hz, AreH), 6.93 (dd, 1H,
J1¼2.1 Hz, J2¼2.1 Hz, AreH), 7.01 (dd, 1H, J1¼2.1 Hz, J2¼2.1 Hz,
AreH), 7.04e7.28 (m, 2H, AreH), 7.30 (d, 1H, J¼15 Hz, O]CeCH]
C), 7.33 (s, 1H, AreH), 7.65 (d, 1H, J¼7.5 Hz, AreH), 7.77 (d, 1H,
J¼15 Hz, O]CeC]CH), 8.03 (d, 1H, J¼8.7 Hz, AreH), 8.81 (s, 1H,
OeCH]C), 10.30 (s, 1H, NH), 10.97 ppm (s, 1H, OH); 13C NMR
4.3.12. (E)-N-(4-Fluorophenyl)-3-(7-methoxy-4-oxo-4H-chromen-3-
yl)acrylamide (5o). Color: yellow; mp: 240.1e240.8 ꢀC; 1H NMR:
(75 MHz, DMSO-d6) d: 102.38, 115.59, 116.37, 118.22, 119.27, 123.20,
(300 MHz, CDCl3)
d
: 3.93 (s, 3H, CH3eO), 6.88 (d, 2H, J¼2.4 Hz,
124.65, 127.25, 128.70, 132.67, 139.47, 156.87, 159.18, 162.90, 164.18,
174.76 ppm; ESI-MS (m/z): 308.10 (Mþ1)þ. Anal. (C18H13NO4): C,
70.35; H, 4.26; N, 4.56. Found: C 70.38, H 4.33, N 4.56%.
AreH), 7.03 (dd, 2H, J1¼1.2 Hz, J2¼2.1 Hz, AreH), 7.37 (d, 1H,
J¼15 Hz, O]CeCH]C), 7.58 (dd, 2H, J1¼5.1 Hz, J2¼5.4 Hz, AreH),
7.70 (d,1H, J¼15 Hz, O]CeC]CH), 8.08 (s,1H, OeCH]C), 8.19 ppm
(d, 1H, J¼9 Hz, AreH); 13C NMR (300 MHz, CDCl3)
d: 55.65, 100.03,
4.3.18. (E)-N-Benzyl-3-(7-hydroxy-4-oxo-4H-chromen-3-yl)acryl-
115.18, 117.23, 118.12, 121.30, 122.51, 125.65, 125.95, 126.32, 128.66,
133.81, 134.76, 156.89, 157.81, 166.24 ppm, 175.55; ESI-MS (m/z):
340.08 (Mþ1)þ. Anal. (C19H14FNO4): C 67.25, H 4.16, N 4.13. Found:
C 67.33, H 4.17, N 4.13%.
amide (5u). Color: yellow; mp: 352.6e253.5 ꢀC; yield: 46%; 1H
NMR: (300 MHz, DMSO-d6)
d
: 4.38 (d, 2H, J¼6 Hz, CH2eAr), 6.88 (d,
1H, J¼2.1 Hz, AreH), 6.95 (dd, 1H, J1¼2.1 Hz, J2¼2.1 Hz, AreH), 7.21
(s, 1H, AreH), 7.23 (d, 1H, J¼2.4 Hz, AreH), 7.23e7.35 (m, 4H, AreH,
O]CeCH]C), 7.40 (d, 1H, J¼15.3 Hz, O]CeC]CH), 7.96 (d, 1H,
J¼8.7 Hz, AreH), 8.63 (s, 1H, OeCH]C), 8.73 (s, 1H, NH), 10.89 ppm
4.3.13. (E)-N-Benzyl-3-(7-methoxy-4-oxo-4H-chromen-3-yl)acryl-
amide (5p). Color: yellow; mp: 257.1e257.5 ꢀC; 1H NMR: (300 MHz,
(s, 1H, OH); 13C NMR (75 MHz, DMSO-d6)
d: 42.22, 102.31, 115.50,
CDCl3)
d
: 3.93 (s, 3H, CH3eO), 4.53 (d, 2H, J¼6 Hz, CH2eAr), 5.96 (s,
116.32, 118.29, 124.36, 126.71, 127.22, 128.25, 131.31, 139.54, 156.87,

9784
Y. Zhang et al. / Tetrahedron 68 (2012) 9777e9787
158.41, 162.80, 165.44, 174.68 ppm; ESI-MS (m/z): 322.09 (Mþ1)þ.
Anal. (C19H15NO4): C 71.02, H 4.71, N 4.36. Found: C 71.05, H 4.75, N
4.38%.
163.91, 165.13, 165.46, 175.47 ppm; ESI-MS (m/z): 426.20 (Mþ1)þ.
Anal. (C26H29NO5): C 71.70, H 6.71, N 3.22. Found: C 71.64, H 6.70, N
3.23%.
4.3.19. (E)-N-(3,4-Difluorobenzyl)-3-(7-hydroxy-4-oxo-4H-chro-
men-3-yl)acrylamide (5v). Color: white; mp: 253.2e253.7 ꢀC; 1H
4.3.24. (E)-N-tert-Butyl-3-(7-methoxy-2-(4-methoxyphenyl)-4-
oxo-4H-chromen-3-yl)acrylamide
(6d). Color:
white;
mp:
NMR: (300 MHz, DMSO-d6)
d
: 4.35 (d, 2H, J¼6 Hz, CH2eAr), 6.87 (d,
131.1e131.5 ꢀC; 1H NMR: (600 MHz, DMSO-d6)
d
: 1.27 (s, 9H, CH3),
1H, J¼2.1 Hz, AreH), 6.94 (dd, 1H, J1¼2.1 Hz, J2¼2.1 Hz, AreH), 7.12
(m, 1H, AreH), 7.21 (s, 1H, AreH), 7.27 (d, 1H, J¼3.3 Hz, AreH),
7.24e7.35 (m, 2H, AreH, O]CeCH]C), 7.40 (d, 1H, J¼15.6 Hz, O]
CeC]CH), 7.96 (d, 1H, J¼8.7 Hz, AreH), 8.63 (s, 1H, OeCH]C),
3.86 (s, 3H, CH3eO), 3.87 (s, 3H, CH3eO), 7.03 (d, 2H, J¼9 Hz,
AreH), 7.08 (d, 1H, J¼15 Hz, O]CeCH]C), 7.11e7.14 (m, 2H,
AreH), 7.51 (d, 1H, J¼15 Hz, O]CeC]CH), 7.60e7.69 (dd, 2H,
J1¼7.2 Hz, J2¼7.8 Hz, AreH), 7.80 (s, 1H, NH), 7.91 ppm (d, 1H,
10.89 ppm (s, 1H, OH); 13C NMR (75 MHz, DMSO-d6)
d
: 42.21,
J¼8.4 Hz, AreH); 13C NMR (75 MHz, DMSO-d6)
d: 28.62, 50.13,
102.29, 115.50, 116.31, 118.29, 124.38, 126.70, 127.22, 128.11, 131.33,
139.54, 156.87, 158.34, 162.42, 165.44, 174.68 ppm; ESI-MS (m/z):
358.08 (Mþ1)þ. Anal. (C19H13F2NO4): C 63.87, H 3.67, N 3.92. Found:
C 63.81, H 3.62, N 3.90%.
55.51, 56.14, 100.42, 114.10, 114.53, 114.97, 116.53, 125.20, 126.78,
127.33, 130.02, 131.55, 156.55, 161.40, 163.88, 165.17, 165.41,
175.47 ppm; ESI-MS (m/z): 408.18 (Mþ1)þ. Anal. (C24H25NO5): C
70.74, H 6.18, N 3.44. Found: C 70.71, H 6.20, N 3.45%.
4.3.20. (E)-N-(4-Fluorophenethyl)-3-(7-hydroxy-4-oxo-4H-chro-
4.3.25. (E)-2-Phenyl-3-styryl-4H-chromen-4-one (6e). Color: yel-
men-3-yl)acrylamide (5w). Color: brown; mp: 217.9e218.3 ꢀC;
low; mp: 168.0e168.5 ꢀC; 1H NMR: (300 MHz, CDCl3)
d: 6.83 (d, 1H,
yield: 77%; 1H NMR: (300 MHz, DMSO-d6)
d: 2.72e2.85 (m, 2H,
J¼16.3 Hz, O]CeCH]C), 7.19e7.57 (m, 10H, AreH), 7.68 (m, 1H,
CH2eAr), 3.35e3.47 (m, 2H, CH2eN), 6.87 (d, 1H, J¼2.1 Hz, AreH),
7.07e7.14 (m, 3H, AreH), 7.19e7.25 (m, 2H, AreH), 7.29 (d, 1H,
J¼15.6 Hz, O]CeCH]C), 7.45 (d, 1H, J¼15.3 Hz, O]CeC]CH), 7.96
(s, 1H, OeCH]C), 8.46 (d, 1H, J¼1.5 Hz, AreH), 8.65 (s, 1H, NH),
AreH), 7.73e7.75 (m, 2H, AreH), 8.03 (d, 1H, J¼16.3 Hz, O]CeC]
CH), 8.32 ppm (d, 1H, J¼8 Hz, AreH); 13C NMR (75 MHz, CDCl3)
d:
105.3, 117.9,118.1,120.4, 123.8, 125.4, 126.5, 126.8, 127.8, 128.8, 130.1,
131.0, 133.5, 133.7, 134.7, 138.5, 155.7, 163.3, 177.7 ppm; ESI-MS (m/
z): 325.11 (Mþ1)þ. Anal. (C23H16O2): C 85.16, H 4.97. Found: C 85.20,
H 4.95%.
10.88 ppm (s, 1H, OH); 13C NMR (75 MHz, DMSO-d6)
d: 34.23, 40.90,
102.40, 115.17, 115.65, 116.38, 118.35, 124.53, 127.16, 127.29, 128.36,
130.53, 135.72, 156.99, 158.41, 162.97, 165.57, 174.84 ppm; ESI-MS
(m/z): 354.11 (Mþ1)þ. Anal. (C20H16FNO4): C 67.98, H 4.56, N 3.96.
Found: C 68.00, H 4.55, N 4.02%.
4.3.26. (E)-3-(7-Methoxy-2-(4-methoxyphenyl)-4-oxo-4H-chromen-
3-yl)-N-phenylacrylamide (6f). Color: yellow; mp: 127.4e127.9 ꢀC;
1H NMR: (600 MHz, DMSO-d6)
d: 3.88 (s, 3H, CH3eO), 3.90 (s, 3H,
4.3.21. (E)-Methyl 3-(7-methoxy-2-(4-methoxyphenyl)-4-oxo-4H-
CH3eO), 7.01e7.04 (t, 1H, AreH), 7.08 (d, 1H, J¼15 Hz, O]CeCH]
C), 7.17e7.19 (m, 2H, AreH), 7.21 (d, 1H, J¼9 Hz, AreH), 7.27e7.30 (t,
3H, AreH), 7.67e7.70 (m, 4H, AreH), 7.77 (d, 1H, J¼15 Hz, O]
CeC]CH), 8.05 (d, 1H, J¼9 Hz, AreH), 10.27 ppm (s, 1H, NH); 13C
chromen-3-yl)acrylate (6a). Color: yellow; mp: 156.2e156.6 ꢀC; 1H
NMR: (600 MHz, DMSO-d6) d: 3.30 (s, 3H, CH3), 3.88 (s, 3H, CH3eO),
3.89 (s, 3H, CH3eO), 7.08e7.10 (dd, 2H, J1¼2.4 Hz, J2¼2.4 Hz, AreH),
7.16e7.19 (m, 2H, AreH), 7.19 (d, 1H, J¼15.6 Hz, O]CeCH]C), 7.33
(d, 1H, J¼15.6 Hz, O]CeC]CH), 7.65e7.67 (m, 2H, AreH),
NMR (75 MHz, DMSO-d6) d: 55.53, 56.18, 100.57, 114.14, 114.26,
115.10, 116.52, 119.13, 123.15, 124.02, 125.65, 126.82, 128.66, 131.72,
132.57, 139.48, 156.61, 161.58, 163.99, 164.36, 166.20, 175.49 ppm;
ESI-MS (m/z): 428.15 (Mþ1)þ. Anal. (C26H21NO5): C 73.06, H 4.95, N
3.28. Found: C 73.08, H 4.90, N 3.31%.
8.01 ppm (d, 1H, J¼9 Hz, AreH); 13C NMR (75 MHz, DMSO-d6)
d:
51.47, 55.63, 56.25, 100.72, 113.67, 114.26, 115.24, 116.49, 120.89,
123.77, 126.91, 131.85, 137.09, 156.64, 161.84, 164.15, 167.11, 167.35,
175.39 ppm; ESI-MS (m/z): 367.11 (Mþ1)þ. Anal. (C21H18O6): C
68.85, H 4.95. Found: C 68.88, H 4.99%.
4.3.27. (E)-N-Benzyl-3-(7-methoxy-2-(4-methoxyphenyl)-4-oxo-4H-
chromen-3-yl)acrylamide (6g). Color: yellow; mp: 220.3e221.0 ꢀC;
4.3.22. (E)-Ethyl
chromen-3-yl)acrylate (6b). Color: white; mp: 157.9e158.3 ꢀC; 1H
NMR: (300 MHz, DMSO-d6) : 1.17e1.22 (t, 3H, CH3eCeO), 3.87
3-(7-methoxy-2-(4-methoxyphenyl)-4-oxo-4H-
1H NMR: (600 MHz, DMSO-d6)
d: 3.87 (s, 3H, CH3eO), 3.89 (s, 3H,
CH3eO), 4.34 (d, 2H, J¼6 Hz, CH2eN), 7.07e7.09 (dd, 1H, J1¼2.4 Hz,
J2¼2.4 Hz, AreH), 7.17 (d, 1H, J¼15.6 Hz, O]CeCH]C), 7.15e7.19
(m, 3H, AreH), 7.21e7.26 (m, 3H, AreH), 7.30e7.32 (m, 2H, AreH),
7.56 (d, 1H, J¼15.6 Hz, O]CeC]CH), 7.55e7.65 (m, 2H, AreH), 8.02
(d, 1H, J¼9 Hz, AreH), 8.70 ppm (s, 1H, NH); 13C NMR (75 MHz,
d
(s, 3H, CH3eO), 3.88 (s, 3H, CH3eO), 4.07e4.14 (q, 2H, CH2eO),
7.07 (d, 1H, J¼9 Hz, AreH) 7.15e7.18 (m, 3H, AreH), 7.26 (d, 1H,
J¼15.9 Hz, O]CeCH]C), 7.33 (d, 1H, J¼15.9 Hz, O]CeC]CH),
7.64e7.66 (m, 2H, AreH), 7.99 ppm (d, 1H, J¼6 Hz, AreH); 13C
DMSO-d6)
d: 42.25, 55.52, 56.17, 100.54, 108.92, 114.11, 115.04,
NMR (75 MHz, DMSO-d6)
d: 14.20, 51.47, 55.31, 56.25, 100.71,
116.53, 124.11, 125.64, 126.73, 126.82, 127.30, 128.26, 131.36, 131.62,
139.56, 156.60, 161.48, 163.94, 165.63, 175.46 ppm; ESI-MS (m/z):
442.16 (Mþ1)þ. Anal. (C27H23NO5): C 73.46, H 5.25, N 3.17. Found: C
73.41, H 5.21, N 3.18%.
113.70, 114.26, 115.24, 116.29, 129.89, 123.18, 126.91, 131.90,
136.79, 156.64, 161.84, 164.15, 167.11, 167.35, 175.51 ppm; ESI-MS
(m/z): 381.12 (Mþ1)þ. Anal. (C22H20O6): C 69.46, H 5.30. Found:
C 69.32, H 3.55%.
4.3.28. (E)-N-(4-Fluorophenethyl)-3-(7-methoxy-2-(4-methox-
4.3.23. (E)-N-Hexyl-3-(7-methoxy-2-(4-methoxyphenyl)-4-oxo-4H-
yphenyl)-4-oxo-4H-chromen-3-yl)acrylamide (6h). Color: yellow;
chromen-3-yl)acrylamide (6c). Color: white; mp: 185.1e185.3 ꢀC;
mp: 186.2e186.8 ꢀC; 1H NMR: (600 MHz, DMSO-d6)
d: 2.71e2.75
1H NMR: (600 MHz, DMSO-d6)
d: 0.83e0.86 (t, 3H, CH3), 1.22e1.27
(t, 2H, CH2eAr), 3.07e3.11 (q, 2H, CH2eN), 3.87 (s, 3H, CH3eO),
3.88 (s, 3H, CH3eO), 7.00e7.03 (m, 2H, AreH), 7.06e7.08 (dd, 1H,
J1¼2.4 Hz, J2¼2.4 Hz, AreH), 7.11 (d, 1H, J¼15.6 Hz, O]CeCH]C),
7.14e7.16 (m, 2H, AreH), 7.17 (d, 1H, J¼2.4 Hz, AreH), 7.23e7.25
(q, 2H, AreH), 7.48 (d, 1H, J¼15 Hz, O]CeC]CH), 7.62e7.64 (m,
2H, AreH), 8.01 (d, 1H, J¼9 Hz, AreH), 8.16e8.18 ppm (t, 1H,
(m, 6H, CH2), 1.38e1.41 (q, 2H, CH2), 3.07e3.11 (q, 2H, CH2), 3.87 (s,
3H, CH3eO), 3.88 (s, 3H, CH3eO), 7.06e7.08 (dd, 2H, J1¼2.4 Hz,
J2¼2.4 Hz, AreH), 7.11 (d, 1H, J¼15 Hz, O]CeCH]C), 7.14e7.16 (q,
2H, AreH), 7.17 (d, 1H, J¼1.8 Hz, AreH), 7.48 (d, 1H, J¼15 Hz, O]
CeC]CH), 7.62e7.64 (q, 2H, AreH), 8.01 (d, 1H, J¼8.4 Hz, AreH),
8.16e8.17 ppm (t, 1H, NH); 13C NMR (75 MHz, DMSO-d6)
d: 13.91,
NH); 13C NMR (75 MHz, DMSO-d6)
d: 34.17, 40.80, 55.52, 56.17,
22.06, 26.16, 29.06, 30.99, 42.59, 55.51, 56.16, 100.51, 114.09, 114.39,
115.02, 116.52, 124.14, 126.06, 126.80, 130.68, 131.60, 156.59, 161.45,
100.53, 114.10, 114.34, 114.80, 115.08, 116.52, 124.12, 125.79,
126.80, 130.32, 130.43, 130.92, 131.60, 135.67, 156.60, 161.46,

Y. Zhang et al. / Tetrahedron 68 (2012) 9777e9787
9785
163.93, 165.60, 175.47 ppm; ESI-MS (m/z): 474.16 (Mþ1)þ. Anal.
(C28H24FNO5): C 71.03, H 5.11, N 2.96. Found: C 71.00, H 5.11, N
2.95%.
175.12 ppm; ESI-MS (m/z): 474.16 (Mþ1)þ. Anal. (C28H24FNO5): C
71.03, H 5.11, N 2.96. Found: C 71.02, H 5.11, N 2.93%.
4.3.34. (E)-Methyl
chromen-3-yl)acrylate (6n). Color: yellow; mp: 331.2e331.8 ꢀC;
1H NMR: (600 MHz, DMSO-d6)
: 3.65 (s, 3H, CH3), 6.86 (d, 1H,
3-(7-hydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-
4.3.29. (E)-Methyl 3-(6,7-dimethoxy-4-oxo-2-phenyl-4H-chromen-
3-yl)acrylate (6i). Color: yellow; mp: 291.1e292.6 ꢀC; 1H NMR:
d
(300 MHz, CDCl3)
d
: 3.75 (s, 3H, CH3), 3.99 (s, 3H, CH3eO), 4.01 (s,
J¼9 Hz, AreH), 6.93e6.95 (dd, 1H, J1¼2.4 Hz, J2¼1.8 Hz, AreH),
6.95e6.98 (m, 2H, AreH), 7.29 (d, 1H, J¼15.6 Hz, O]CeCH]C),
7.32 (d, 1H, J¼15.6 Hz, O]CeC]CH), 7.52e7.54 (m, 2H, AreH),
7.95 (d, 1H, J¼9 Hz, AreH), 10.33 (s, 1H, OH), 10.86 ppm (s, 1H,
3H, CH3eO), 6.92 (s, 1H, AreH), 7.46 (d, 1H, J¼15.9 Hz, O]CeCH]
C), 7.53 (d, 1H, J¼15.9 Hz, O]CeC]CH), 7.55e7.59 (m, 3H, AreH),
7.62 (s, 1H, AreH), 7.63e7.67 ppm (m, 2H, AreH); 13C NMR
(75 MHz, CDCl3)
d
: 51.45, 55.93, 56.53, 100.61, 113.97, 114.52,
OH); 13C NMR (75 MHz, DMSO-d6)
d: 51.46, 101.53, 113.75,
116.034, 116.21, 119.95, 123.77, 126.91, 131.25, 137.09, 153.53,
161.58, 164.05, 167.11, 167.35, 175.05 ppm; ESI-MS (m/z): 367.11
(Mþ1)þ. Anal. (C21H18O6): C 69.46, H 5.30. Found: C 69.31, H
3.55%.
114.22, 120.89, 123.60, 126.88, 131.89, 137.16, 156.61, 161.51,
164.24, 167.11, 167.63, 175.35 ppm; ESI-MS (m/z): 339.08
(Mþ1)þ. Anal. (C19H14O6): C 67.45, H 4.17. Found: C 67.41, H
4.21%.
4.3.30. (E)-N-tert-Butyl-3-(6,7-dimethoxy-4-oxo-2-phenyl-4H-chro-
4.3.35. (E)-Ethyl
chromen-3-yl)acrylate (6o). Color: white; mp: 319.3e319.9 ꢀC; 1H
NMR: (600 MHz, DMSO-d6) 1.19e1.21 (t, 3H, CH3eCeO),
3-(7-hydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-
men-3-yl)acrylamide (6j). Color: white; mp: 243.9e245.3 ꢀC; 1H
NMR: (600 MHz, DMSO-d6)
d
: 1.26 (s, 9H, CH3), 3.88 (s, 3H, CH3eO),
d:
3.90 (s, 3H, CH3eO), 7.06 (d, 1H, J¼15.6 Hz, O]CeCH]C), 7.26 (s,
1H, AreH), 7.43 (s, 1H, AreH), 7.51 (d, 1H, J¼15.6 Hz, O]CeC]CH),
7.60e7.67 (m, 5H, AreH), 7.80 ppm (s, 1H, NH); 13C NMR (75 MHz,
4.10e4.13 (q, 2H, CH2eO), 6.87 (d, 1H, J¼2.4 Hz, AreH), 6.94e6.95
(dd, 1H, J1¼2.4 Hz, J2¼1.8 Hz, AreH), 6.96e6.97 (m, 2H, AreH), 7.27
(d, 1H, J¼15.9 Hz, O]CeCH]C), 7.33 (d, 1H, J¼15.9 Hz, O]CeC]
CH), 7.53e7.54 (m, 2H, AreH), 7.96 (d, 1H, J¼9 Hz, AreH), 10.33 (s,
DMSO-d6) d: 28.61, 51.31, 55.81, 56.42, 100.32, 114.35, 114.80, 115.21,
116.68, 125.40, 126.78, 127.33, 130.02, 130.95, 156.52, 161.40, 164.15,
165.17, 165.22, 175.04 ppm; ESI-MS (m/z): 408.18 (Mþ1)þ. Anal.
(C24H25NO5): C 70.74, H 6.18, N 3.44. Found: C 70.72, H 6.20, N
3.44%.
1H, OH), 10.86 ppm (s, 1H, OH); 13C NMR (75 MHz, DMSO-d6)
d:
14.15, 59.80, 102.21, 113.02, 115.47, 120.70, 122.16, 127.24, 131.91,
137.28, 156.50, 160.51, 163.94, 166.91, 167.19, 175.32 ppm; ESI-MS
(m/z): 353.11 (Mþ1)þ. Anal. (C20H16O6): C 68.18, H 4.58. Found: C
68.11, H 4.69%.
4.3.31. (E)-3-(6,7-Dimethoxy-4-oxo-2-phenyl-4H-chromen-3-yl)-N-
phenylacrylamide (6k). Color: yellow; mp: 264.5e265.5 ꢀC; 1H
4.3.36. (E)-N-Hexyl-3-(7-hydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-
NMR: (300 MHz, DMSO-d6)
d
: 3.90 (s, 3H, CH3eO), 3.91 (s, 3H,
chromen-3-yl)acrylamide (6p). Color: white; mp: 273.9e274.4 ꢀC;
CH3eO), 7.00e7.05 (t, 1H, AreH), 7.23e7.30 (m, 3H, AreH), 7.28
(d, 1H, J¼15.6 Hz, O]CeCH]C), 7.46 (s, 1H, AreH), 7.46e7.73 (m,
7H, AreH), 7.787 (d, 1H, J¼15.3 Hz, O]CeC]CH), 10.33 ppm (s,
1H NMR: (600 MHz, DMSO-d6)
d: 0.83e0.85 (t, 3H, CH3), 1.21e1.27
(m, 6H, CH2), 1.37e1.41 (q, 2H, CH2), 3.07e3.10 (q, 2H, CH2), 6.86
(d, 1H, J¼1.8 Hz, AreH), 6.92e6.96 (m, 3H, AreH), 7.11 (d, 1H,
J¼15.6 Hz, O]CeCH]C), 7.45 (d, 1H, J¼15.6 Hz, O]CeC]CH),
7.49e7.50 (q, 2H, AreH), 7.94 (d, 1H, J¼9 Hz, AreH),
1H, NH); 13C NMR (75 MHz, DMSO-d6)
d: 55.83, 56.46, 100.49,
103.98, 114.41, 115.92, 116.25, 119.19, 123.15, 125.86, 128.66,
129.75, 131.12, 132.04, 132.42, 139.42, 147.71, 151.00, 154.59,
164.26, 165.86, 175.06 ppm; ESI-MS (m/z): 428.15 (Mþ1)þ. Anal.
(C26H21NO5): C 73.06, H 4.95, N 3.28. Found: C 73.08, H 4.90, N
3.31%.
8.10e8.12 ppm (t, 1H, NH); 13C NMR (75 MHz, DMSO-d6)
d: 13.89,
22.04, 26.14, 29.04, 30.95, 40.23, 102.51, 106.26, 113.52, 114.31,
115.32, 116.52, 124.14, 126.46, 126.80, 130.68, 131.55, 156.52,
160.25, 162.80, 165.52, 175.47 ppm; ESI-MS (m/z): 408.18 (Mþ1)þ.
Anal. (C24H25NO5): C 70.74, H 6.18, N 3.44. Found: C 70.69, H 6.17,
N 3.39%.
4.3.32. (E)-N-Benzyl-3-(6,7-dimethoxy-4-oxo-2-phenyl-4H-chro-
men-3-yl)acrylamide (6l). Color: yellow; mp: 223.3e223.8 ꢀC; 1H
NMR: (600 MHz, DMSO-d6)
d: 3.90 (s, 3H, CH3eO), 391 (s, 3H,
4.3.37. (E)-N-tert-Butyl-3-(7-hydroxy-2-(4-hydroxyphenyl)-4-oxo-
CH3eO), 4.33 (d, 2H, J¼6 Hz, CH2eN), 7.17 (d, 1H, J¼15.6 Hz, O]
CeCH]C), 7.22e7.26 (m, 3H, AreH), 7.28 (s, 1H, AreH), 7.30e7.33
(t, 2H, AreH), 7.46 (s, 1H, AreH), 7.58 (d, 1H, J¼15.6 Hz, O]CeC]
CH), 7.61e7.65 (m, 3H, AreH), 7.68e7.70 (d, 2H, J¼6 Hz, AreH),
4H-chromen-3-yl)acrylamide
(6q). Color:
white;
: 1.26 (s, 9H, CH3),
mp:
322.4e322.9 ꢀC; 1H NMR: (300 MHz, DMSO-d6)
d
6.84 (d, 2H, J¼2.1 Hz, AreH), 6.91e6.97 (m, 3H, AreH), 7.06 (d, 1H,
J¼15.6 Hz, O]CeCH]C), 7.46e7.51 (m, 3H, AreH, O]CeC]CH),
7.81 (s, 1H, NH), 7.95 (d, 1H, J¼8.7 Hz, AreH), 10.26 (s, 1H, OH),
8.72e8.74 ppm (t, 1H, NH); 13C NMR (75 MHz, DMSO-d6)
d: 42.27,
55.85, 56.47, 100.48, 104.02, 114.48, 115.95, 125.82, 126.75, 127.33,
128.27, 128.67, 129.70, 131.05, 131.28, 132.14, 139.53, 147.70, 151.01,
154.58, 165.49, 165.58, 175.11 ppm; ESI-MS (m/z): 442.16 (Mþ1)þ.
Anal. (C27H23NO5): C 73.46, H 5.25, N 3.17. Found: C 73.41, H 5.21, N
3.18%.
10.83 ppm (s, 1H, OH); 13C NMR (75 MHz, DMSO-d6)
d: 28.61, 50.12,
102.20, 114.08, 114.53, 114.27, 115.48, 125.20, 127.38, 127.33, 130.02,
131.68, 156.58, 160.25, 163.88, 165.36, 165.65, 175.48 ppm; ESI-MS
(m/z): 380.14 (Mþ1)þ. Anal. (C22H21NO5): C, 69.64; H, 5.58; N,
3.69. Found: C 69.49, H 5.55, N 3.66%.
4.3.33. (E)-3-(6,7-Dimethoxy-4-oxo-2-phenyl-4H-chromen-3-yl)-N-
4.3.38. (E)-3-(7-Hydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-
(4-fluorophenethyl)acrylamide
(6m). Color:
yellow;
: 2.71e2.74 (t, 2H,
mp:
3-yl)-N-phenylacrylamide (6r). Color: yellow; mp: 318.9e319.6 ꢀC;
275.1e276.6 ꢀC; 1H NMR: (600 MHz, DMSO-d6)
d
1H NMR: (600 MHz, DMSO-d6)
d
: 6.87 (d, 1H, J¼2.4 Hz, AreH),
CH2eAr), 3.31e3.34 (q, 2H, CH2eN), 3.87 (s, 3H, CH3eO), 389 (s, 3H,
CH3eO), 7.08 (d, 1H, J¼15.6 Hz, O]CeCH]C), 7.09 (d, 1H, J¼3 Hz,
AreH), 7.12 (s, 1H, AreH), 7.21e7.23 (q, 2H, AreH), 7.24 (s, 1H,
AreH), 7.42 (s, 1H, AreH), 7.44 (d, 1H, J¼15 Hz, O]CeC]CH),
7.59e7.62 (m, 5H, AreH), 8.26e8.28 ppm (t, 1H, NH); 13C NMR
6.95e6.96 (dd, 1H, J1¼2.4 Hz, J2¼2.4 Hz, AreH), 6.96e6.99 (m, 2H,
AreH), 7.01e7.03 (t, 1H, AreH), 7.28 (d, 1H, J¼15.6 Hz, O]CeCH]
C), 7.27e7.29 (t, 2H, AreH), 7.54e7.56 (m, 2H, AreH), 7.69 (d, 2H,
J¼7.8 Hz, AreH), 7.75 (d, 1H, J¼15.6 Hz, O]CeC]CH), 7.99 (d, 1H,
J¼8.4 Hz, AreH), 10.26 (s, 1H, NH), 10.33 (s, 1H, OH), 10.85 ppm (s,
(75 MHz, DMSO-d6)
d: 40.75, 55.85, 56.48, 100.46, 104.03, 114.52,
1H, OH); 13C NMR (75 MHz, DMSO-d6)
d: 102.19, 106.43, 113.67,
114.83, 115.10, 115.96, 126.03, 128.67, 129.72, 130.33, 130.44, 130.86,
131.04, 132.19, 135.66, 147.70, 151.02, 154.58, 165.35, 165.57,
115.47, 119.15, 122.50, 123.13, 125.19, 127.22, 128.67, 131.85, 133.01,
139.53, 156.54, 160.32, 162.87, 164.52, 166.43, 175.48 ppm; ESI-MS

9786
Y. Zhang et al. / Tetrahedron 68 (2012) 9777e9787
(m/z): 400.11 (Mþ1)þ. Anal. (C24H17NO5): C 72.17, H 4.29, N 3.51.
d6) d: 24.33, 25.14, 48.43, 102.21, 106.43, 113.48, 114.96, 115.30,
Found: C 72.14, H 4.22, N 5.58%.
116.32, 124.11, 126.46, 126.16, 130.68, 131.34, 156.52, 160.23, 162.80,
165.50, 175.50 ppm; ESI-MS (m/z): 392.14 (Mþ1)þ. Anal.
(C23H21NO5): C 70.58, H 5.41, N 3.58. Found: C 70.42, H 5.38, N
3.52%.
4.3.39. (E)-N-Benzyl-3-(7-hydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-
chromen-3-yl)acrylamide (6s). Color: yellow; mp: 279.1e279.5 ꢀC;
1H NMR: (600 MHz, DMSO-d6)
d
: 4.34 (d, 2H, J¼6 Hz, CH2eN), 6.86
(d, 1H, J¼1.8 Hz, AreH), 6.93e6.96 (m, 3H, AreH), 7.18 (d, 1H,
J¼15 Hz, O]CeCH]C), 7.21e7.26 (m, 3H, AreH), 7.30 (d, 1H,
J¼15 Hz, O]CeC]CH), 7.31 (s, 1H, AreH), 7.51e7.55 (m, 3H, AreH),
7.96 (d,1H, J¼8.4 Hz, AreH), 3.67e8.69 (t,1H, NH),10.26 (s,1H, OH),
4.3.44. (E)-7-Hydroxy-2-(4-hydroxyphenyl)-3-(3-oxo-3-(1H-pyr-
azol-1-yl)prop-1-enyl)-4H-chromen-4-one (6x). Color: yellow; mp:
297.1e297.7 ꢀC; 1H NMR: (300 MHz, DMSO-d6)
d: 6.63e6.65 (q, 1H,
pyrazole), 6.90 (d, 1H, J¼2.1 Hz, AreH), 6.95e7.00 (m, 3H, AreH),
7.58e7.64 (m, 3H, AreH, pyrazole, O]CeCH]C), 7.95 (d, 1H,
J¼6 Hz, AreH), 7.97 (d, 1H, J¼15.3 Hz, O]CeC]CH), 8.43e8.44 (t,
1H, AreH), 8.75 (d, 1H, J¼15.6 Hz, pyrazole), 10.56 ppm (s, 2H, OH);
10.81 ppm (s, 1H, OH); 13C NMR (75 MHz, DMSO-d6)
d: 42.23,
102.16, 106.94, 114.02, 115.44, 116.53, 122.46, 125.37, 125.18, 126.73,
126.82, 127.70, 128.28, 131.36, 131.75, 139.61, 156.51, 160.23, 164.44,
165.86, 175.46 ppm; ESI-MS (m/z): 414.15 (Mþ1)þ. Anal.
(C25H19NO5): C 72.63, H 4.63, N 3.39. Found: C 72.60, H 4.60, N
3.39%.
13C NMR (75 MHz, DMSO-d6)
d: 102.22, 106.28, 110.43, 113.64,
115.47, 119.27, 123.13, 125.19, 129.53, 131.85, 133.01, 144.63, 156.54,
160.32, 162.87, 164.52, 166.43, 175.44 ppm; ESI-MS (m/z): 375.09
(Mþ1)þ. Anal. (C21H14NO5): C 67.38, H 3.77, N 7.48. Found: C 67.44,
H 3.71, N 7.42%.
4.3.40. (E)-N-(4-Fluorophenethyl)-3-(7-hydroxy-2-(4-hydrox-
yphenyl)-4-oxo-4H-chromen-3-yl)acrylamide (6t). Color: yellow;
mp: 165.2e165.8 ꢀC; 1H NMR: (300 MHz, DMSO-d6)
d: 2.70e2.75 (t,
Acknowledgements
2H, CH2eAr), 3.29e3.32 (q, 2H, CH2eN), 6.86 (s, 1H, AreH),
6.92e6.97 (m, 3H, AreH), 7.07e7.15 (m, 3H, AreH, O]CeCH]C),
7.21e7.26 (q, 2H, AreH), 7.46 (d, 1H, J¼15.6 Hz, O]CeC]CH), 7.51
(d, 2H, J¼8.7 Hz, AreH), 7.95 (d, 1H, J¼8.7 Hz, AreH), 8.25e8.28 (t,
1H, NH), 10.32 (s, 1H, OH), 10.84 ppm (s, 1H, OH); 13C NMR (75 MHz,
This work was supported by the National Natural Science
Foundation of China (Grant No. 21172259) and Shanghai Rising-Star
Program (Grant No. 09QA1407000). We also thanks to the Key
Laboratory of Drug Research for special environments, PLA.
DMSO-d6) d: 34.17, 40.80, 102.16, 106.34, 113.61, 114.55, 114.80,
115.45, 116.52, 123.20, 125.33, 127.40, 130.32, 130.43, 130.92, 131.72,
135.67, 156.53, 160.26, 161.80, 165.60, 175.47 ppm; ESI-MS (m/z):
446.15 (Mþ1)þ. Anal. (C26H20FNO5): C 70.11, H 4.53, N 3.14. Found: C
70.19, H 4.56, N 3.25%.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2012.09.017. These data in-
clude MOL files and InChIKeys of the most important compounds
described in this article.
4.3.41. (E)-N-Cyclohexyl-3-(7-hydroxy-2-(4-hydroxyphenyl)-4-oxo-
4H-chromen-3-yl)acrylamide
(6u). Color:
yellow;
: 1.02e1.31 (m, 4H,
mp:
287.6e288.4 ꢀC; 1H NMR: (300 MHz, DMSO-d6)
d
References and notes
cyclohexane), 1.54 (d, 2H, J¼11.4 Hz, cyclohexane), 1.65e1.75 (t, 4H,
cyclohexane), 3.58 (d, 1H, J¼7.2 Hz, cyclohexane), 6.85 (d, 1H,
J¼2.1 Hz, AreH), 6.91e6.96 (m, 3H, AreH), 7.11 (d, 1H, J¼15.6 Hz,
O]CeCH]C), 7.47 (d, 1H, J¼15.6 Hz, O]CeC]CH), 7.49e7.52 (m,
2H, AreH), 7.96 (d, 1H, J¼9 Hz, AreH), 8.07 (d, 1H, J¼7.8 Hz, NH),
10.30 (s, 1H, OH), 10.81 ppm (s, 1H, OH); 13C NMR (75 MHz, DMSO-
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